Rh-Negative and Rh-Positive Conditions in Pregnancy

As a practicing obstetrician, I’m happy to report the good news—today almost all pregnancies complicated by Rh-negative concerns do well. When you are pregnant, the old adage is true: good fences do make good neighbors. Your blood and your developing baby’s blood remain separate, and the membrane that separates them maintains a peaceful coexistence until delivery. Here’s how your body is very well designed to protect you and your baby.

How The Placenta Protects

The placenta is the membrane attached to your uterus that separates your blood from your baby’s blood. The placenta lets some things through but not others, and there is a size limitation on what can pass freely between baby and you. So smaller things like oxygen and carbon dioxide molecules have no trouble, but bigger, bulkier structures such as bacteria or red blood cells are blocked. In this way, oxygen can pass through this barrier from your red blood cells to your baby’s red blood cells without the two types of cells entering the others’ domains and setting off a huge immunological response, or allergic reaction. It works well, but there are some holes in the system.

What Invading Antigens Do

Your entire immune system depends on its ability to fight foreigners, called antigens. Your body makes antibodies when an antigen gets into your system. The antibodies you make for you are small, though—small enough to slip through the placenta. This is a good thing, because it allows your baby to be protected at birth with a host of your antibodies with which to fight off infection during the first few months of life.

Invading antigens, however, are usually attached to bigger structures, like red blood cells. These are too bulky to pass between your baby and you. Your baby’s red blood cells, usually different from the type you have—thanks to that big foreign body, your husband—can’t get to you, and neither can the antigens they carry. The separation of your and your baby’s circulations means there is no mixing of your two different blood types. You aren’t exposed to your baby’s red blood cells and you won’t generate antibodies to your baby’s blood. This is good because if you did, these antibodies made to fight your baby’s red blood cells would be small enough to get back to your baby. Inheriting your antibodies to fight infections is one thing, but your baby inheriting antibodies to herself is another thing altogether—a dangerous thing.

There’s a small detail I haven’t mentioned yet—that little process called giving birth. During your baby’s birth, the placenta barrier is broken up, allowing a brief opportunity for your red blood cells and your baby’s to mix. The importance of this brief mixing doesn’t necessarily apply to the baby just delivered, but to future babies, as I’ll explain later.

Blood Types and Antigens

People identify their blood types as A, B, AB, or O. ABO is the main blood cell antigen system. But there’s also the CDE system. Each of these systems refers to a type of red blood cell antigen that identifies itself as an enemy or a friend as reliably as a serviceman’s uniform. So, blood types are called A, B, or AB, because they have the A-, B-, or both the A- and B-antigens.

Different blood types just don’t get along very well. That’s because antigens will generate an allergic reaction in a person given a different blood type. In the most severe cases, getting blood that doesn’t match yours could cause an allergic reaction leading to death. While these instances are rare, A, B, or O reactions between you and your baby occur often when the two blood streams mix briefly at birth. But this response is usually mild.

The Rh Factor and Blood Incompatibility

In pregnancy, the Rh hoopla centers around the “D” antigen of the CDE system. This antigen is called the Rhesus D because the initial research was done with Rhesus monkeys. If you have D-antigen-type red blood cells, you’re “Rh-positive.” If you don’t, you’re “Rh-negative.” The reaction to D—the Rh antigen—can be very serious.

If you and your baby are Rh-negative, there’s no problem, since you both have the same Rh type. If you’re Rh-negative and your baby is Rh-positive (thanks to your husband’s genes), that’s fine until your blood mixes with your baby’s blood a bit during placental separation at birth. At that critical point, fetal blood cells can accidentally combine with your system, and you make antibodies to fight them. Your immune system is successful in vanquishing these stray fetal blood cells in your circulation. This is of no consequence, because once they’ve gotten rid of the baby’s blood cells in your system, they have no other job. And they can’t filter back through to your baby’s blood, because delivery has already taken place. The antibodies you made just remain in your circulation waiting. For what? For your next pregnancy. Herein lies the problem.

Rh, Fetal Anemia, and RhoGam

Your antibodies to Rh-positive red blood cells last a long time. In fact, they last long enough and are small enough to be able to pass through to your next baby, and they will do just that. As stated above, the ABO allergic reaction is mild. But if you’re Rh-negative and your last baby was Rh-positive, you’ve made anti-Rh antibodies. And you’ll be sending those anti-Rh antibodies through the placenta into your next baby. The fetal red blood cells that house the Rh-antigen will be attacked and over time your baby will lose these blood cells, becoming anemic. This isn’t good in a baby who’s trying to grow and mature. Such anemia can cause swelling reactions in the baby’s abdomen and eventually can cause serious injury or fetal death. This condition is referred to as “erythroblastalis fetalis.”

The prevention of erythroblastalis fetalis is another victory of modern obstetrics. The condition is rare today because we give an injection soon after delivery, called RhoGam, to first-time Rh-negative mothers of Rh-positive babies. These are the mothers who we know will be making antibodies to their subsequent baby’s blood. RhoGam is also an anti-Rh-positive antibody. For moms who receive RhoGam, their bodies are fooled into thinking there’s already been an adequate response and make no antibodies on their own. So now the antibodies of RhoGam don’t attack subsequent babies because they’re much bigger molecules than what you would have produced on your own and can’t pass through the placenta to your next baby. It’s this preventative measure that has so greatly reduced the risk of erythroblastalis fetalis.

But what if you’re Rh-negative and didn’t get this RhoGam shot after your last baby? If the last baby was also Rh-negative, there was no antigen-antibody conflict and all is well for your next baby. In fact, hospitals routinely check your newborn’s blood type and if your baby is Rh-negative like you, there’s no need to get the RhoGam shot at all. But if you’re Rh-negative and your baby were Rh-positive and you didn’t get the shot, the shot didn’t work well (almost unheard of), or was given too late to prevent you from making antibodies (there’s about a three-day window), then your next baby may be at risk of severe anemia as your antibodies cross the placenta barrier and begin attacking his or her red blood cells.

How can you tell if a baby is getting anemic from such a condition? If your history suggests such a risk or if telltale signs on ultrasound suggest erthroblastalis fetalis, an amniocentesis can be done. This is a technique in which amniotic fluid around your baby is withdrawn with a thin needle under ultrasound guidance and is then studied. In cases of erythroblastalis fetalis, the fluid becomes murky. This is because there’s a lot of bilirubin in it, which is a breakdown product of exploded red blood cells. By this method it can be determined how serious the condition is.

The Best News of All

In the past, babies with erthroblastalis fetalis were just out of luck. Such a pregnancy often resulted in a “stillbirth,” a vague term at best. A wide range of unrelated conditions, from genetic malformations to umbilical cord knots, could all result in stillbirths. The Rh factor was identified in 1940. In the mid 1960s, the RhoGam shot was developed and began being clinically tested. At that time, 14 percent of Rh-negative mothers developed antibodies to their subsequent babies. Doctors started giving RhoGam routinely by the late 1960s, and soon, the chances fell to 1.8 percent. But even the 1.8 percent was too much. So now RhoGam is given not only after delivery, but also at 28 weeks gestation—well before delivery. This early treatment is in case there is some “silent” bleeding—too scant to be noticed, but enough to develop antibodies during a current pregnancy. Now the 1.8 percent has been reduced to 0.07 percent (less than one in a thousand).

That is why today almost all Rh-negative concerns during pregnancy can be relieved. And usually it’s as simple as A-B-C…and a little RhoGam.

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